Genetic Variant NM_001348946.2:c.2685+3559C>T (chr7-87527735-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001348946.2(ABCB1):c.2685+3559C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,072 control chromosomes in the GnomAD database, including 8,745 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 8745 hom., cov: 32)

Consequence

ABCB1
NM_001348946.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.539

Publications

33 publications found

Variant links:

Genes affected

ABCB1 (HGNC:40): (ATP binding cassette subfamily B member 1) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ABCB1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348946.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCB1	NM_001348946.2	MANE Select	c.2685+3559C>T	intron	N/A	NP_001335875.1	P08183-1
ABCB1	NM_001348945.2		c.2895+3559C>T	intron	N/A	NP_001335874.1
ABCB1	NM_000927.5		c.2685+3559C>T	intron	N/A	NP_000918.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.2685+3559C>T	intron	N/A	ENSP00000478255.1	P08183-1
ABCB1	ENST00000265724.8	TSL:1	c.2685+3559C>T	intron	N/A	ENSP00000265724.3	P08183-1
ABCB1	ENST00000488737.6	TSL:1	n.327+3559C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43914

AN:

151954

Hom.:

8714

Cov.:

show subpopulations

Gnomad AFR

AF:

0.555

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.436

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.232

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.264

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.289

AC:

44000

AN:

152072

Hom.:

8745

Cov.:

AF XY:

0.287

AC XY:

21297

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.555

AC:

23020

AN:

41462

American (AMR)

AF:

0.240

AC:

3660

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

730

AN:

3468

East Asian (EAS)

AF:

0.435

AC:

2249

AN:

5170

South Asian (SAS)

AF:

0.220

AC:

1062

AN:

4818

European-Finnish (FIN)

AF:

0.112

AC:

1183

AN:

10582

Middle Eastern (MID)

AF:

0.243

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.165

AC:

11198

AN:

67998

Other (OTH)

AF:

0.268

AC:

565

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1400

2800

4201

5601

7001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.218

Hom.:

8998

Bravo

AF:

0.313

Asia WGS

AF:

0.339

AC:

1175

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.1

(source)

DANN

Benign

0.41

PhyloP100

-0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over